Our objective is the achievement of chemical enhancement of radiation injury to tumors of the nervous system. A series of agents will be tested in experimental models of gliomas and schwannomas currently operational in our laboratories. Tumor cells for testing will be derived from our present group of seven cell lines, developed from nitrosourea treated rats and including examples of astrocytoma, mixed astro-oligodendrocytoma, gliosarcoma, spongioblastoma, and schwannoma. In addition, clones of similarly derived neoplastic astrocytes and Schwann cells are available from a collaborator. All of these lines will be subject to careful morphological and biochemical characterization. One experimental model will consist of an intracerebral brain tumor system in syngeneic rats, which will be studied for the endpoint of host survival time and tumor cell colony forming efficiency. Another model will involve an in vitro system in which cultures of the cell lines will be irradiated and survival curves plotted on the basis of dye exclusion method of surviving cell counts as well as colony forming efficiency. For initial phase of this study, cell lethality is the primary object of interest. Groups of chemicals to be investigated are chosen on the basis of known features of these tumors. These agents will include lysosomal labilizers and membrane altering compounds (Vitamin A, Filipin), high electron affinity compounds (nitroheterocyclic compounds), agents decreasing reduced glutathione (diamide and also nitrofurans), and pentose pathway inhibitor (6-amino-nicotinamide). BIBLIOGRAPHIC REFERENCES: Allen, N., Clendenon, N.R., Abe, H., Swenberg, J.A., Koestner, A., Wechsler, W., and Shuttleworth, E.C.: Acid Hydrolase and Cytochrome Oxidase Activities In Nitrosourea Induced Tumors of the Nervous System. Acta Neuropath. 1977, in press. Allen, N., Clendenon, N.R., Denlinger, R., and Kartha, M.K.: Effect of Vitamin A on Radiation Enhancement and Survival in Experimental Rat Gliomas. Trans. Amer. Neurol. Assoc., 1977, in press.